The Impact of Cardiac Radiation Dosimetry on Survival After Radiation Therapy for Non-Small Cell Lung Cancer

Int J Radiat Oncol Biol Phys. 2017 Sep 1;99(1):51-60. doi: 10.1016/j.ijrobp.2017.04.026. Epub 2017 Apr 27.

Abstract

Purpose: The heart receives high radiation doses during radiation therapy of advanced-stage lung cancer. We have explored associations between overall survival, cardiac radiation doses, and electrocardiographic (ECG) changes in patients treated in IDEAL-CRT, a trial of isotoxically escalated concurrent chemoradiation delivering tumor doses of 63 to 73 Gy.

Methods and materials: Dosimetric and survival data were analyzed for 78 patients. The whole heart, pericardium, AV node, and walls of left and right atria (LA/RA-Wall) and ventricles (LV/RV-Wall) were outlined on radiation therapy planning scans, and differential dose-volume histograms (dDVHs) were calculated. For each structure, dDVHs were approximated using the average dDVH and the 10 highest-ranked structure-specific principal components (PCs). ECGs at baseline and 6 months after radiation therapy were analyzed for 53 patients, dichotomizing patients according to presence or absence of "any ECG change" (conduction or ischemic/pericarditis-like change). All-cause death rate (DR) was analyzed from the start of treatment using Cox regression.

Results: 38% of patients had ECG changes at 6 months. On univariable analysis, higher scores for LA-Wall-PC6, Heart-PC6, "any ECG change," and larger planning target volume (PTV) were significantly associated with higher DR (P=.003, .009, .029, and .037, respectively). Heart-PC6 and LA-Wall-PC6 represent larger volumes of whole heart and left atrial wall receiving 63 to 69 Gy. Cardiac doses ≥63 Gy were concentrated in the LA-Wall, and consequently Heart-PC6 was highly correlated with LA-Wall-PC6. "Any ECG change," LA-Wall-PC6 scores, and PTV size were retained in the multivariable model.

Conclusions: We found associations between higher DR and conduction or ischemic/pericarditis-like changes on ECG at 6 months, and between higher DR and higher Heart-PC6 or LA-Wall-PC6 scores, which are closely related to heart or left atrial wall volumes receiving 63 to 69 Gy in this small cohort of patients.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Analysis of Variance
  • Carcinoma, Non-Small-Cell Lung / diagnostic imaging
  • Carcinoma, Non-Small-Cell Lung / mortality*
  • Carcinoma, Non-Small-Cell Lung / radiotherapy*
  • Cause of Death
  • Dose Fractionation, Radiation
  • Electrocardiography / radiation effects
  • Female
  • Heart / diagnostic imaging
  • Heart / physiology
  • Heart / radiation effects*
  • Heart Atria / diagnostic imaging
  • Heart Atria / radiation effects
  • Humans
  • Lung Neoplasms / diagnostic imaging
  • Lung Neoplasms / mortality*
  • Lung Neoplasms / radiotherapy*
  • Male
  • Middle Aged
  • Organs at Risk / diagnostic imaging
  • Organs at Risk / physiology
  • Organs at Risk / radiation effects*
  • Pericardium / radiation effects
  • Principal Component Analysis
  • Prospective Studies
  • Radiation Dosage
  • Radiation Injuries / mortality*
  • Radiation Injuries / physiopathology
  • Radiotherapy Planning, Computer-Assisted